The Role of Lipid Interactions in Simulations of the ?-Hemolysin Ion-Channel-Forming Toxin.

ABSTRACT: Molecular dynamics simulations were performed to describe the function of the ion-channel-forming toxin ?-hemolysin (?HL) in lipid membranes that were composed of either 1,2-diphytanoyl-sn-glycero-3-phospho-choline or 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline. The simulations highlight the importance of lipid type in maintaining ?HL structure and function, enabling direct comparison to experiments for biosensing applications. We determined that although the two lipids studied are similar in structure, 1,2-diphytanoyl-sn-glycero-3-phospho-choline membranes better match the hydrophobic thickness of ?HL compared to 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline membranes. This hydrophobic match is essential to maintaining proper alignment of ?-sheet loops at the trans entrance of ?HL, which, when disrupted, creates an additional constriction to ion flow that decreases the channel current below experimental values and creates greater variability in channel conductance. Agreement with experiments was further improved with sufficient lipid membrane equilibration and allowed the discrimination of subtle ?HL conduction states with lipid type. Finally, we explore the effects of truncating the extramembrane cap of ?HL and its role in maintaining proper alignment of ?HL in the membrane and channel conductance. Our results demonstrate the essential role of lipid type and lipid-protein interactions in simulations of ?HL and will considerably improve the interpretation of experimental data.

SUBMITTER: Guros NB 

PROVIDER: S-EPMC6225056 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature